Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy-Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling

Author(s):Show less -

Li, Wei Bo ^[1] ; Stangl, Stefan ^{[2, 3]} ; Klapproth, Alexander ^{[1, 2, 3]} ; Shevtsov, Maxim ^{[2, 3, 4, 5]} ; Hernandez, Alicia ^{[2, 3]} ; Kimm, Melanie A. ^{[6, 7]} ; Schuemann, Jan ^{[8, 9]} ; Qiu, Rui ^[10] ; Michalke, Bernhard ^[11] ; Bernal, Mario A. ^[12] ; Li, Junli ^[7] ; Huerkamp, Kerstin ^[1] ; Zhang, Yibao ^[13] ; Multhoff, Gabriele ^{[2, 3]}

Affiliation:Show less -

^[1] German Res Ctr Environm Hlth GmbH, Inst Radiat Med, Helmholtz Zentrum Munchen, D-85764 Neuherberg - Germany

^[2] Tech Univ Munchen TranslaTUM, Klinikum Rechts Isar, Ctr Translat Canc Res, Einsteinstr 25, D-81675 Munich - Germany

^[3] Technishe Univ Munchen TUM, Klinikum Rechts Isar, Dept Radiat Oncol, Ismaningerstr 22, D-81675 Munich - Germany

^[4] Almazov Natl Med Res Ctr, Personalized Med Ctr, 2 Akkuratova Str, St Petersburg 197341 - Russia

^[5] Russian Acad Sci RAS, Lab Biomed Nanotechnol, Inst Cytol, Tikhoretsky Ave 4, St Petersburg 194064 - Russia

^[6] Tech Univ Munchen TUM, Klinikum Rechts Isar, Dept Diagnost & Intervent Radiol, D-81675 Munich - Germany

^[7] Ludwig Maximilians Univ Munchen, Dept Radiol, Univ Hosp, D-81337 Munich - Germany

^[8] Harvard Med Sch, Boston, MA 02114 - USA

^[9] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Phys, Boston, MA 02114 - USA

^[10] Tsinghua Univ, Dept Engn Phys, Beijing 100084 - Peoples R China

^[11] German Res Ctr Environm Hlth GmbH, Res Unit Analyt BioGeoChem, Helmholz Zentrum Munchen, D-85764 Neuherberg - Germany

^[12] Univ Estadual Campinas, Gleb Wataghin Inst Phys, BR-13083859 Campinas, SP - Brazil

^[13] Peking Univ Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ, Dept Radiat Oncol, Beijing 100142 - Peoples R China

• Document type: Journal article
• Source: CANCERS; v. 13, n. 21 NOV 2021.
• Web of Science Citations: 0

Abstract

Simple Summary: High-Z gold nanoparticles show potential as radiosensitizers in the radiotherapy of cancer. In this paper, we introduce the benefits and procedures for the application of gold nanoparticles in targeted cancer radiotherapy. Based on microscopic images of the distribution of antibody-conjugated nanoparticles, we established pharmacokinetic models simulating the biodistribution of nanoparticle conjugates in the tumor and tumor environment in preclinical models. This information has been implemented in radiation transport Monte Carlo simulation codes for further investigating physical and chemical enhancement and radiobiological effects, such as DNA strand breaks and cell survival. Future perspectives and challenges of translating this promising gold nanoparticle-aided radiotherapy into clinical practice are also discussed.</p> High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum Munchen. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.</p> (AU)

• FAPESP's process: 15/21873-8 - Establishment and application of methodologies for optimizing imaging techniques in digital radiology
• Grantee: Alessandra Tomal
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/08647-7 - Developments of X-ray characterization techniques and application in quantitative neuroscience
• Grantee: Jean Rinkel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/51594-2 - Development of a computational system for the simulation of the interaction of ionizing radiations with the human genetic material
• Grantee: Mario Antonio Bernal Rodriguez
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/15316-7 - Study of the interaction of heavy charged particles with DNA using computational methods
• Grantee: Mario Antonio Bernal Rodriguez
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2